Visual and tear function MURAT DOGRU. CHIKAKO KATAKAMI, MASATO MIYASHITA, ETSUKO HIDA, improvement after MAMORU UENISHI, KAZUAKI TETSUMOTO, SANAE KANNO, superficial TERUO NISHIDA, AKIO YAMANAKA phototherapeutic keratectomy (PTK) for mid-stromal corneal scarnng

M. Dogru Abstract Key words Corneal sensitivity, Interferometry, M. Miyashita Phototherapeutic keratectomy, Tear film, Tear H. Hida Purpose To study the changes in visual and film lipid layer M. Uenishi tear film function following superficial A. Yamanaka excimer laser phototherapeutic keratectomy in Department of patients with mid-stromal corneal scars. Excimer lasers have enabled ophthalmologists Kobe Kaisei Hospital Kobe, Japan Methods Fourteen eyes of 14 patients with to treat superficial corneal pathologies more efficiently. The available excimer laser systems mid-stromal corneal scars seen at the C. Katakami Department of Ophthalmology at Kobe Kaisei remove corneal tissue not only with extreme Department of Ophthalmology Hospital underwent superficial precision but with minimal adjacent tissue Kobe University School of phototherapeutic keratectomy (PTK). The damage. Increased interest in excimer laser Medicine subjects underwent routine ophthalmic Kobe, Japan phototherapeutic keratectomy (PTK) in the mid- examinations, corneal sensitivity 1980s stimulated several experimental and K. Tetsumoto measurements, tear film break-up time (BUT), clinical studies reporting successful removal of Department of Ophthalmology Schirmer test and tear film lipid layer Shakai Hoken Kobe Chuo superficial opacities from the corneal visual axis interferometry. Thirty eyes of 15 normal Hospital and attainment of smooth regular surfaces. Such control subjects were also studied. The Kobe, Japan studies also report visually satisfactory results patients and the control subjects were following PTK of a wide variety of superficial S. Kanno compared for pre-PTK tear function Department of corneal opacities. Although PTK has been parameters and tear film lipid layer Ophthalmology proven to be successful in the management of interferometry grade. The alterations in these Hyogo College of Medicine superficial corneal opacities, keratoplasty Hyogo, Japan parameters within 6 months following PTK procedures are widely accepted as appropriate were also determined. T. Nishida for deeper corneal involvement. Results Visual improvement was achieved in Department of Ophthalmology We aimed to study whether PTK would be 12 eyes (86%). A hyperopic shift was observed Yamaguchi University beneficial in patients with mid-stromal corneal School of Medicine in all eyes. The average pre-PTK corneal scars in whom a keratoplasty procedure could Ube, Japan sensitivity and tear film BUT were lower in not be performed. Therefore, we performed patients compared with control subjects Chikako Katakami, MD, PhD t'!'l , , corneal sensitivity, tear before PTK. Tear film lipid layer Department of Ophthalmology film break-up time, tear film lipid layer Kobe University School of interferometry grades were also higher in the interferometry and Schirmer test Medicine patients than the controls before PTK. All measurements; comparing the results with 7-5-2 Kusunokicho, Chuoku these parameters improved gradually and Kobe650-0017, Japan those of normal control subjects and also significantly after PTK. Schirmer test results Tel: +81 78 3826048 looking at the early alterations in these did not show any significant alterations after Fax: +81 78 3826059 parameters within 6 months after PTK. PTK. Proprietary interest: None Conclusion We conclude that PTK is an effective means of treating corneal scars and This work was presented at Materials and methods the 22nd Mid-Japan attaining visual improvement, even in cases Congress of Subjects and examinations with deeper corneal involvement, and may Ophthalmology, 21 obviate the need for corneal transplantation. Fourteen eyes of 14 patients with deep corneal November 1999, Kyoto, Simultaneous improvements in corneal scars (9 men, 5 women) between 34 and 86 years Japan sensitivity and tear film stability suggest of age (mean 68.6 ± 11.9 years) underwent Received: 20 December 1999 favourable effects of PTK on the ocular excimer laser PTK at Kobe Kaisei Hospital Eye Accepted in revised form: surface. Clinic between September 1998 and September 13 April 2000

Eye (2000) 14, 779-784 © 2000 Royal College of Ophthalmologists 779 Table 1. Clinical features of the patients Best corrected Central Ablation visual acuity Patient Sex/Age Follow-up corneal depth (D) no. (years) Aetiology (months) thickness (fim) (J.Lm) Initial Final Initial Final

1 M/65 Herpetic 15 422 :+: 7 90 -1.75 c-1.0 X 60° +1.00 c-1.5 X 75° 20/25 20/16 2 M/34 Unknown 12 402 :+: 4 70 +0.50 c-0.75 X 80° +1.50 c-0.50 X 85° 20/100 20/32 3 M/73 Post-infectious 12 504 :+: 2 100 -1.75 c-1.25 X 90° +2.00 c-1.5 X 105° 20/200 20/63 4 F/63 Traumatic 9 593 :+: 4 120 -3.00 +3.00 20/200 20/100 5 F/71 Traumatic 13 511 :+: 2 120 Not measurable :+:5.00 HM 20/200 6 F/74 Traumatic 9 496 :+: 4 100 Not measurable +2.00 HM 20/200 7 M/62 Herpetic 7 517 :+: 8 100 Not measurable +4.00 HM 20/100 8 M/69 Unknown 14 638 :+: 12 120 -1.50 +4.50 20/200 20/63 9 M/86 Unknown 7 498 :+: 4 90 +2.00 c+0.50 X 175° +5.00 c+0.75 X 5° 20/63 20/50 10 M/59 Post-infectious 6 494 :+: 6 90 Not measurable +2.50 HM 20/200 11 M/61 Herpetic 6 486 :+: 2 120 -1.00 +3.00 20/200 20/200 12 F/64 Traumatic 6 SOl:+: 3 90 -6.00 -3.00 20/200 20/20 13 F/66 Herpetic 11 520 :+: 8 120 -1.00 +5.50 20/200 20/200 14 M/66 Traumatic 8 558 :+: 14 120 Not measurable +3.75 HM 20/200

1999. The aetiologies of the corneal opacities are shown complete blink and the appearance of the first corneal in Table 1. All patients underwent routine ophthalmic black spot in the stained tear film was measured three examinations including best corrected Landolt visual times and the mean value of the measurements was acuity, slit-lamp microscopy, anterior segment calculated. A BUT value of less than 10 s was considered photography, Eye Sys corneal topography, pachymetry, abnormal. fundoscopy, Cochet-Bonnet corneal sensitivity The tear film status and the lipid layer were also measurement, tear film break-up time, tear film lipid evaluated by a DR-l interferometer system (Kowa, layer interferometry and a Schirmer test, which were Japan). The principles of the system using interference performed before PTK as well as 1 week, 1 month, 3 patterns has been described elsewhere. 1 The tear lipid months and 6 months after PTK. A careful examination layer interference patterns have been classified by Yokoi of the lid margins was also conducted. All examinations et al. into five grades: grade 1, somewhat grey colour, and gradings were performed by the same researcher. uniform distribution; grade 2, grey colour, non-uniform Thirty eyes of 15 age- and sex-matched healthy distribution; grade 3, few colours, non-uniform individuals were taken as controls. Informed consent for distribution; grade 4, many colours, non-uniform the procedures was obtained. All patients were also distribution; grade 5, corneal surface partially exposed. questioned about the presence of symptoms of eye Grade 3 and above were regarded as indicators of a dry fatigue, dryness and irritation before and 6 months after eye state as reported previously. 1 The patients were PTK. None of the patients had a history of Stevens­ instructed not to instil their medications for at least 6 h Johnson syndrome, of chemical, thermal or radiation before tear film lipid layer interferometry measurements. injury, or of any ocular disease except the corneal The measurements were carried out at the same time opacity. Patients and control subjects also did not have interval following the last complete blink in all patients. any history of systemic diseases, or of drug or contact For further evaluation of tears, the standard Schirmer use, and had not undergone any ocular surgery that test with topical anaesthesia (0.4% oxybuprocaine would create an ocular surface problem. chloride) was performed. The standardised strips of filter Measurement of corneal sensitivity was performed by paper (Alcon, Texas) were placed in the lateral canthus using a Cochet-Bonnet aesthesiometer. The away from the and left in place for 5 min with the measurements were begun with the nylon filament eyes closed. Readings were reported in millimetres of (<1>0.12mm) fully extended. The tip of the filament was wetting for 5 min. A reading of less than 5 mm was supplied perpendicularly to the surface of the central referred to as dry eye. cornea making certain not to touch the eye lashes, and was pushed until the fibre's first visibly bent. The length The PTK procedure of the fibre was gradually decreased until a blink reflex was observed. The length was recorded in units of Due to a long waiting list for penetrating keratoplasty in millimetres. A corneal sensitivity measurement of less Japan, only those patients with mid-stromal corneal scars than 40 mm was regarded as low. who consented to a trial of excimer laser corneal ablation The standard tear film break-up time (BUT) initially, until fresh donor cornea became available, measurement was performed. Moistened fluorescein underwent the PTK procedure. The transepithelial strips were introduced into the conjunctival sac with corneal ablations were carried out using the Nidek-EC minimal stimulation and were undetected by the 5000 excimer laser under topical 0.4% oxybuprocaine patients. The subjects were then instructed to blink anaesthesia. We used a 5-6.0 mm ablation zone, several times for a few seconds to ensure adequate 70-120 fLm ablation depth and a pulse frequency of mixing of fluorescein. The interval between the last 30Hz.

780 A transition zone (TZ) of 1 mm was set in all eyes. Sodium hyaluronate 0.1% was applied as necessary during the procedures to achieve a smoother ablation. The patients were fitted with soft therapeutic contact lenses at the end of the procedure and were prescribed topical ofloxacin and sodium hyaluronate eye drops until corneal epithelisation. The patients were then put on fluorometholone 0.1% and ofloxacin eye drops for 6 months, after which they were gradually tapered. Those patients who developed subepithelial corneal haze were evaluated by the Fantes grading system and were prescribed betamethasone 0.1 % eye drops. Patients with a history of herpetic received oral acyclovir (a) 1000 mg/ day before and for 3 weeks after PTK to prevent any recurrence.

Statistical analysis

Data were processed using StatView software (1988, Abacus Concepts, San Diego, CAl. The Mann-Whitney test was used for the analyses of non-parametric values. A probability level less than 1% was considered statistically significant. The analysis of categorical data was performed by Fisher's exact probability test, with the probability level set at 1 % for statistical significance.

(b)

Fig. 1. Herpetic corneal scar: (a) before PTK, (b) 8 months after PTK. Results

Clinical features Refractive outcome None of the eyes had pre-operative corneal epithelial erosions in this study. All patients complained of All patients had a hyperopic shift ranging between +1.0 and +6.5 D (mean 3.98 ± 1.81 D) following PTK. Five symptoms of eye fatigue, dryness and irritation which patients in whom post-operative anisometropia became a disappeared after PTK. All eyes had complete and problem were successfully managed with gas-permeable uneventful corneal re-epithelisation within 3 days hard wear. Post-PTK Eye Sys corneal following PTK. Four patients developed Fantes Grade II topography and pachymetry did not reveal corneal subepithelial haze 3--4 months after PTK which ectasia in any of the patients. Corneal topography disappeared within 6 months. No visually disabling showed gradual central corneal flattening for 3 months complications related to PTK were observed. Recurrence which stabilised afterwards. of active herpetic disease was not encountered in this study.

Corneal sensitivity

The average pre-PTK corneal sensitivity was Visual outcome 39.1 ± 5.5 mm in the patients compared with Best corrected visual acuity improved in 12 eyes despite 58.3 ± 0.6 mm in the control subjects, as shown in Table 2 the presence of some degree of corneal stromal opacity (p < 0.001). Thirteen eyes (93%) had a Cochet-Bonnet after PTK. A representative case is shown in Fig. 1. Six corneal sensitivity recording of less than 40 mm pre­ eyes (43%) had an improvement of more than 2 lines and operatively. There were no eyes with a low corneal 2 eyes (14%) had an improvement of 1 line of Landolt sensitivity reading 6 months after PTK. Corneal corrected visual acuity. Two eyes showed no change in sensitivity showed a statistically significant increase at visual acuity following PTK. One of these 2 eyes had the first, third and sixth post-PTK months, as shown in myopic macular chorioretinal atrophy and the other had Fig. 2 (p < 0.001). The patients with herpetic leucoma cellophane . Visual acuity increased from tended to have a slower recovery and the corneal hand movements to 20/100 or 20/200 in 4 eyes (29%). sensitivity measurements were slightly lower at the 6 Worsening of visual acuity was not encountered in any month follow-up examination compared with other patient (Table 1). patients (Table 3).

781 Corneal sensitivity (mm) Table 2. Comparison of pre-PTK corneal sensitivity and tear function parameters between patients and control subjects 65 �------,

* Patients Controls * 60 T Corneal sensitivity (mm) 39.1:!: 5.5 58.3:!: 0.6* Tear film break-up time (s) 6.5:!: 2.4 14.0 :!: 1.2* 55 Schirmer test (mm) 6.5:!: 1.7 11.5:!: 0.6 Tear film lipid layer 3.5:!: 0.4 1.2:!: 0.4* 50 interferometry grade 45 *p < 0.001; Mann-Whitney test.

40 Tear function parameters 35 The pre-PTK tear function parameters of the patients and the control subjects are summarised in Table 2. Mean 30�-----.-----.-----.-----.-----,-----; Pre PTl< t week 1 month 3 months 6 months pre-PTK values of the BUT test were 6.5 ± 2.4 s in the post PTl< postPTl< post PTl< post PTl< patients and 14.0 ± 1.2 s in the control group. The < difference was statistically significant (p < 0.001). All eyes Fig. 2. Change in corneal sensitivity after PTK. *p 0.001, Fisher's exact test. in this study had a pre-PTK BUT score of less than 10 s. On the other hand, only 1 eye displayed a low BUT score 6 months after PTK. The tear film BUT showed disappointing for deeper corneal involvement, which is shortening at the first post-operative week which then traditionally approached with penetrating or lamellar prolonged significantly at the first, third and sixth post­ keratoplasty.6-9 We have previously reported that operative months as shown in Fig. 3 (p < 0.001). Tear film excimer laser PTK has favourable effects on the health of lipid layer interferometry showed smoothing of the the ocular surface in a variety of corneal opacities corneal surface with a regular tear film distribution after including Avellino, lattice and granular corneal PTK (Fig. 4). The average tear film lipid layer dystrophy, and superficial corneal interference grade before PTK was 3.5 ± 0.4 in the scars.lO We aimed to study the visual and tear film patients and 1.2 ± 0.4 in the control subjects (p < 0.001). changes in 14 patients with mid-stromal corneal scarring No eye showed a pre-PTK grade 1 or 2 (normal) tear film in whom a keratoplasty procedure could not be interferometry pattern whereas all eyes revealed normal performed within a short period of time due to a long grading at the sixth post-operative month. The tear film waiting list for penetrating keratoplasty in Japan and interferometry grading showed a statistically significant who consented to an initial trial of a PTK procedure until gradual improvement 1 month, 3 months and 6 months fresh donor cornea became available. after PTK as shown in Fig. 5 (p < 0.001). We attained visual improvement in 12 eyes (86%) and Pre-PTK Schirmer test value averaged 6.5 ± 1.7 mm in saw that PTK could obviate the need for keratoplasty. the patients versus 11.5 ± 0.6 mm in the controls Two patients who had no change in their visual acuity (p > 0.001). The pre-PTK and first week, first month, third after PTK still reported a clearer vision compared with month and sixth month post-PTK Schirmer test values their pre-PTK status. All eyes ended up with a hyperopic were 6.5 ± 1.7 mm, 6.3 ± 1.9 mm, 6.1 ± 0.7 mm, refraction after PTK in this series. Five patients 6.6 ± 1.1 mm and 6.4 ± 1.3 mm respectively. Post­ developed anisometropia due to induced hyperopia and operative Schirmer test results did not show any were successfully managed with gas-permeable hard significant differences. contact lens wear. A hyperopic shift is commonly observed after PTK and remains a major problem. The difference in the energy distribution due to shielding by Discussion the debris of the photoablation, difference of the ablation Many studies on PTK have reported beneficial results in rates between central and peripheral cornea, corneal a wide variety of pre-operative diagnoses. Amongst epithelial and stromal healing responses have all been these, corneal scars represent one group where it is not implicated as possible explanations for the hyperopic always easy to place an indication for PTK?-S While PTK shiftY-13 Controlled long-term studies on the effect of can be visually rewarding for superficial corneal factors such as ablation depth, ablation zone diameter, opacities, visual outcome can be variable and sometimes transition zone setting, masking agent use, epithelial

Table 3. Aetiology-specific comparison of corneal sensitivity (mm) before and after PTK After PTK Aetiology of corneal scar Before PTK 1 week 1 month 3 months 6 months

Traumatic (n = 5 eyes) 44.0 :!: 2.6 50.0:!: 2.4 57.8:!: 2.7 58.5:!: 2.1 58.4:!: 2.3

Herpetic (n = 4 eyes) 31.5:!: 2.5 31.0 :!: 2.8 45.6 :!: 1.4 47.8 :!: 1.2 48.0 :!: 2.4

Post-infectious (n = 2 eyes) 37.5:!: 3.5 42.5:!: 3.5 56.2 :!: 1.7 57.5 :!: 3.5 58.5:!: 2.1

Unknown (n = 3 eyes) 40.0:!: 1.8 45.0 :!: 1.6 57.6:!: 1.1 58.3 :!: 2.8 59.0:!: 1.7

782 seconds Grade

20 5

*

15 4

*

10 I 3 * 1

2

Pre PTK 1 week 1 month 3 months 6 months Pre PTK 1 week 1 month 3 mon1hs 6 months postPTK post PTl< post PTl< post PTK postPTK postPTK post PTK postPTK

Fig. 3. Change in tear film break-up time after PTK. *p < 0.001, Fig. 5. Change in tear film lipid layer interferometry grade after PTK. Fisher's exact test. *p < 0.001, Fisher's exact test. hyperplasia and subepithelial haze on induced similar to dry eye states.16 Through careful clinical and hyperopia would provide very interesting information. ophthalmological examination, we ruled out the We also noted that symptoms of eye fatigue and possibility of systemic lipid disorders, Meibomian gland irritation dramatically improved after PTK in all patients. dysfunction or aqueous tear deficiency as the cause of We attributed such symptomatology to the presence of a 4 5 higher grades of interference patterns. It has been BUT-deficient dry eye state.1 ,1 as described by Lemp reported that mucin-lipid interaction is required for the and Barsam et al. and the irregularity of the corneal Meibomian lipids to spread uniformly over the surface before PTK. Indeed, the tear film was significantly unstable in the patients compared with the outermost surface of the tear film. Mucin might control subjects and tear stability improved remarkably coacervate at the surface of the corneal epithelium and be within 6 months after PTK. This, we believe, was mainly gradually diluted towards the surface of the tear film. due to attainment of a regular corneal surface and a Thus the three layers of the tear film might not be clearly 7 better epithelium-tear film interaction following PTK. distinguishable.1 This might explain the gradual Another explanation may be the change in quantity improvement in BUT scores and interference pattern and/ or quality of mucin secretion by a healthier corneal grades, which we attribute to a better mucin-lipid layer epithelium after re-epithelisation. Tear film mucin interaction after achievement of a regular corneal quantification before and after PTK would be very epithelial surface and probably mucin secretion by a interesting. One other piece of evidence for improvement of the tear film after PTK came from tear film lipid layer functionally healthier corneal epithelium. However, interferometry measurements. Our patients had higher further studies on the alterations of the lipid layer and its grades of interferometry examinations before PTK, components in dry eyes should be carried out.

(a) (b)

Fig.4. Tear film surface observed by tear filminterferometry in a patient with traumatic corneal leucoma. (a) Irregularity of the corneal surface and tear film distribution before PTK. (b) Regular corneal surface and tear film distribution attained 3 months after PTK.

783 Finally, another interesting finding was that the 5. Sher NA, Bowers RA, Zabel RW. Clinical use of the 193-nm excimer laser in the treatment of corneal scars. Arch corneal sensitivity gradually improved after PTK. OphthalmoI1991;109:491-8. Corneal nerves have been shown to start regenerating 6. Migden M, Elkins B, Clinch TE. Phototherapeutic within 24 h after PTK. A significantly lower pre-PTK keratectomy for corneal scars. Ophthalmic Surg Lasers corneal sensitivity in the patients strongly implied 1996;27:0503-7. epithelial and stromal disease. Given that the ablation 7. Fagerholm P, Ohman L, Orndahl M. Phototherapeutic depth varied between 70 and 120 j.Lm in this group of keratectomy in . Acta Ophthalmol 1994;72:457-60. patients, we presume that we were able to remove the 8. Campos M, Nielsen S, Szerenyi K, Garbus JJ, McDonnell PJ. epithelial and subepithelial corneal nerve plexus. Clinical follow up of phototherapeutic keratectomy for Improvement in corneal sensitivity within 6 months after treatment of corneal opacities. Am J Ophthalmol PTK suggested that uneventful corneal regeneration took 1993;115:433--40. place in our patients, similar to the findings in other 9. Fagerholm P, Fitzsimmons TD, Omdahl M, Ohman 1, 1& 20 reports. - Tengroth B. Phototherapeutic keratectomy: long term results Corneal nerves are said to maintain the health of the in 166 eyes. J Refract Corneal Surg 1993;9:S76-81. 21 22 10. Dogru M, Katakami C. Miyashita M, Hida E, Uenishi M, ocular surface through their trophic action. , We Tetsumoto K, et al. Ocular surface changes after excimer laser believe that an increased corneal sensitivity should have phototherapeutic keratectomy. Ophthalmology favourable effects on the milieu of corneal epithelial cells 2000;107:1144-52. and corneal stroma. One other interesting finding was 11. Fantes FE, Hanna KD, Waring GO III. Wound healing after that the improvement in corneal sensitivity was excimer laser keratomileusis (photorefractive keratectomy) in comparatively slower in patients with herpetic corneal monkeys. Arch Ophthalmol 1990;108:665-75. scar. Indeed, decreased corneal sensitivity has been 12. Liu C. Hyperopic shift and the use of masking agents in excimer laser superficial keratectomy [letter]. reported in patients with herpetic keratitis and the extent Br J Ophthalmol 1992;76:62-3. of recovery of corneal sensitivity has been related to the 13. Amm M, Duncker GIW. Refractive changes after 23 severity of corneal involvement. Whether a delayed phototherapeutic keratectomy. J Refract Surg healing response is specific or not for herpetic leucomas 1997;23:839--44. after PTK waits to be answered by longer and larger 14. Lemp MA. Dry eye syndromes: treatment and clinical trials. controlled studies, In: Lacrimal gland, tear film and . New York: Plenum Press, 1994. Concurrent improvements in corneal sensitivity, 15. Barsam PL, Sampson WG, Feldman GL. Treatment of the dry visual and tear film function were attained in this set of eye and related problems. Ann Ophthalmol 1972;4:122-9. patients with mid-stromal corneal scarring. We conclude 16. Danjo Y, Hamano T. Observation of precorneal tear film in that PTK is a relatively safe and effective means of patients with Sjogren's syndrome. Acta Ophthalmol Scand treating corneal scars and that visual improvement can 1995;73:501-5. be attained even in cases with mid-stromal corneal 17. Holly FJ. Formation and rupture of the tear film. Exp Eye Res involvement despite the presence of some degree of 1973;15:515-25. 18. Linna T, Tervo T. Real-time confocal microscopic remaining . In this sense, PTK may also observations on human corneal nerves and wound healing offer an alternative to corneal transplantation. We after excimer laser photorefractive keratectomy. Curr Eye therefore believe in the necessity of further and broader Res 1997;16:640-9. case-controlled clinicopathological studies in this field. 19. Ishikawa T, Kanai A, Aquavella JV, et al. Correlation between corneal sensitivity and nerve regeneration following excimer laser ablation. J Jpn Ophthalmol Soc 1995;2:135-42. References 20. Trabucci G, Brancato R. Verdi M, et al. Corneal nerve damage 1. Yokoi N, Takehisa Y, Kinoshita S. Correlation of tear lipid and regeneration after excimer laser photokeratectomy in layer interference patterns with the diagnosis and severity of rabbit eyes. Invest Ophthalmol Vis Sci 1994;35:229-35. dry eye. Am J Ophthalmol 1996;122:814-28. 21. Tseng SCG, Hirst LW, Maumenee AE, et al. Possible 2. Thompson VM. Excimer laser phototherapeutic keratectomy: mechanisms for the loss of goblet cells in mucin-deficient clinical and surgical aspects. Ophthalmic Surg Lasers disorders. Ophthalmology 1984;91:545-52. 1995;26:461-72. 22. Tseng SCG, Hirst LW, Farazdagi M, Green WR. Goblet cell 3. Hersh PS, Spinak A, Garrana R, Mayers M. Phototherapeutic density and vascularisation during conjunctival keratectomy: strategies and results in 12 eyes. Refract transdifferentiation. Invest Ophthalmol Vis Sci Corneal Surg 1993;9:S90-5. 1984;25:1168-76. 4. Thompson V, Durrie DG, Cavanaugh TB. Philosophy and 23. Norn MS. Dendritic herpetic keratitis. IV. Follow-up technique for excimer laser phototherapeutic keratectomy. examination of corneal sensitivity. Acta Ophthalmol Refract Corneal Surg 1993;9:581-5. 1970;48:383-95.

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